Epilepsy, affecting 0.5-2% of the population worldwide, is one of the most common neurological disorders. While the characteristic electrical activity in the epileptic cortex has been extensively studied, the mechanisms underlying epileptogenesis are poorly understood. Focal neocortical epilepsy often develops following traumatic, ischemic or infectious brain injury. Under these conditions, local compromise of blood-brain barrier (BBB) integrity is common, as revealed by ultrastructural studies of animal and human epileptic tissue in multiple forms of epilepsy, raising the possibility that primary vascular damage, and specifically BBB opening, may serve as an initial event leading to epilepsy. This hypothesis has been confirmed by animal studies, in which opening of the BBB was sufficient to induce delayed epileptiform activity. Subsequent studies have shown that albumin, the most common serum protein, is sufficient to recapitulate the epileptiform activity induced by BBB disruption, and that albumin is selectively taken up by astrocytes (Ivens et al., 2007).